chr10-101580324-G-A

Variant names:

• chr10-101580324-G-A
• rs41562219
• NM_001174084.2:c.1287C>T

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_001174084.2(POLL):​c.1287C>T​(p.Asp429Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00597 in 1,613,988 control chromosomes in the GnomAD database, including 57 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0040 (4 hom., cov: 33)
  • Exomes 𝑓: 0.0062 (53 hom.)
• Consequence: POLL NM_001174084.2 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.292

Genes affected

POLL (HGNC:9184): (DNA polymerase lambda) This gene encodes a DNA polymerase. DNA polymerases catalyze DNA-template-directed extension of the 3'-end of a DNA strand. This particular polymerase, which is a member of the X family of DNA polymerases, likely plays a role in non-homologous end joining and other DNA repair processes. Alternatively spliced transcript variants have been described. [provided by RefSeq, Mar 2010]

DPCD (HGNC:24542): (deleted in primary ciliary dyskinesia homolog (mouse)) This gene in mouse encodes a protein that may be involved in the generation and maintenance of ciliated cells. In mouse, expression of this gene increases during ciliated cell differentiation, and disruption of this gene has been linked to primary ciliary dyskinesia. [provided by RefSeq, Jul 2016]

ACMG classification

Our verdict: Benign. The variant received -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.52).
• BP6: Variant 10-101580324-G-A is Benign according to our data. Variant chr10-101580324-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3024781.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.292 with no splicing effect.
• BS2: High Homozygotes in GnomAd4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
POLL	NM_001174084.2	c.1287C>T	p.Asp429Asp	synonymous_variant	Exon 8 of 9	ENST00000370162.8	NP_001167555.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
POLL	ENST00000370162.8	c.1287C>T	p.Asp429Asp	synonymous_variant	Exon 8 of 9	1	NM_001174084.2	ENSP00000359181.3

Frequencies

GnomAD3 genomes AF: 0.00404 AC: 615 AN: 152192 Hom.: 4 Cov.: 33

Gnomad AFR AF: 0.00253

Gnomad AMI AF: 0.00219

Gnomad AMR AF: 0.00399

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000188

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.00642

Gnomad OTH AF: 0.00239

GnomAD2 exomes AF: 0.00352 AC: 884 AN: 251400 AF XY: 0.00346

Gnomad AFR exome AF: 0.00160

Gnomad AMR exome AF: 0.00295

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000554

Gnomad NFE exome AF: 0.00629

Gnomad OTH exome AF: 0.00472

GnomAD4 exome AF: 0.00617 AC: 9017 AN: 1461678 Hom.: 53 Cov.: 33 AF XY: 0.00591 AC XY: 4299 AN XY: 727154

Gnomad4 AFR exome AF: 0.00161 AC: 54 AN: 33480

Gnomad4 AMR exome AF: 0.00291 AC: 130 AN: 44714

Gnomad4 ASJ exome AF: 0.000115 AC: 3 AN: 26136

Gnomad4 EAS exome AF: 0.00 AC: 0 AN: 39700

Gnomad4 SAS exome AF: 0.0000232 AC: 2 AN: 86254

Gnomad4 FIN exome AF: 0.000807 AC: 43 AN: 53314

Gnomad4 NFE exome AF: 0.00762 AC: 8472 AN: 1111920

Gnomad4 Remaining exome AF: 0.00497 AC: 300 AN: 60392

GnomAD4 genome AF: 0.00403 AC: 614 AN: 152310 Hom.: 4 Cov.: 33 AF XY: 0.00383 AC XY: 285 AN XY: 74466

Gnomad4 AFR AF: 0.00250 AC: 0.00250084 AN: 0.00250084

Gnomad4 AMR AF: 0.00398 AC: 0.0039838 AN: 0.0039838

Gnomad4 ASJ AF: 0.00 AC: 0 AN: 0

Gnomad4 EAS AF: 0.00 AC: 0 AN: 0

Gnomad4 SAS AF: 0.00 AC: 0 AN: 0

Gnomad4 FIN AF: 0.000188 AC: 0.000188324 AN: 0.000188324

Gnomad4 NFE AF: 0.00643 AC: 0.00642534 AN: 0.00642534

Gnomad4 OTH AF: 0.00237 AC: 0.00236967 AN: 0.00236967

Alfa AF: 0.00540 Hom.: 1

Bravo AF: 0.00422

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.00731

EpiControl AF: 0.00729

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Feb 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

POLL: BP4, BP7, BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.52
CADD	Benign	0.16
DANN	Benign	0.88
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs41562219; hg19: chr10-103340081; COSMIC: COSV105159539;